In Singapore, breast cancer remains the most frequently diagnosed cancer and the principal cause of cancer-related deaths among women. According to the data from the Singapore Cancer Registry Annual Report 2021, between 2017 and 2021, breast cancer was identified as the most common cancer among women, with 12,735 cases diagnosed in the five-year period. It alone constituted approximately 30% of all female cancer diagnoses and was responsible for nearly 17% (2,304 cases) of all female cancer deaths.

Beyond that, the likelihood of developing breast cancer escalates significantly after the age of 30 and peaks during the 60s. Among Singapore's various ethnic groups, the Chinese population shows a higher age-standardised incidence rate compared to Malays and Indians. In addition, according to the same study by the Singapore Cancer Registry Annual Report, from 2017 to 2021, breast cancer was the predominant cancer diagnosed across all ethnic groups, making up about 29-35% of all cases. Particularly in the age group of 40 to 49 years, it accounted for nearly half of all cancer diagnoses.

Singapore's diverse population, encompassing various ethnicities with unique languages, cultural practices, dietary habits, and clothing styles, reflects the complexity of understanding breast cancer. Just as the population is diverse, so too are the subtypes of breast cancer identified among patients. Broadly, there are hormone receptor-positive breast cancer, HER2-positive breast cancer and triple-negative breast cancers. They have certain unique characteristics and behaviours. These tumour subtypes were classified initially by gene tests known as expression profiling, highlighting the genetic underpinnings that influence their development and response to treatment.

What is Triple-Negative Breast Cancer?

Triple negative (or triple-negative) breast cancer is increasingly being studied, and some information may change as more is known about this type of breast cancer.

TNBC is defined by the absence of three key receptors known to fuel most breast cancer growth: oestrogen (or estrogen) receptors (ER), progesterone receptors (PR) or human epidermal growth factor receptor 2 (HER2).

When a breast tumour is tested, the presence or absence of these receptors determines the type of cancer. In TNBC, the cancer cells test negative for ER, PR, and HER2, which means they do not respond to hormonal therapies such as those targeting oestrogen or progesterone, nor to therapies that target HER2. This lack of receptors contributes to the aggressive nature of TNBC, as it tends to grow and spread more quickly than other breast cancer types.

Additionally, TNBC is more likely to metastasise beyond the breast and has a higher likelihood of recurrence after treatment, which makes its management challenging. Despite these difficulties, understanding TNBC is crucial as it accounts for a relatively large percentage of all invasive breast cancer cases.

What is Triple-Positive Breast Cancer and How is it Different?

According to the National Cancer Institute, this type of breast cancer is characterised by tumours that express oestrogen receptors, progesterone receptors, and an increased number of HER2 receptors. This subtype of breast cancer can be addressed with a combination of hormone therapies and drugs that specifically target the HER2 receptor, providing a tailored approach to treatment. The presence of these receptors offers more options for effective therapies, often leading to better management of the disease.

In contrast to triple-negative breast cancer, which tends to be more aggressive due to the lack of these receptors, triple-positive breast cancer can be identified and managed based on its receptor status. While triple-negative cancers are often associated with a younger age at diagnosis, more advanced stages at presentation, and a higher likelihood of recurrence and metastasis, triple-positive cancers can benefit from targeted therapies that tap into their receptor positivity.

Key Insights into Triple-Negative Breast Cancer

Some features and commonly asked questions about triple-negative breast cancer (TNBC) include:

1. Who Tends to Get Triple-Negative Breast Cancer?

They seem to occur in higher frequency in younger women and may be associated with a higher likelihood of BRCA1 gene expression.

Women of African or Hispanic ancestry also seem to have a higher rate of triple-negative breast cancer. TNBC in Asian breast cancer patients have not been as well studied. However, our own group and others have shown many of these are young breast cancer patients, and many may be related to BRCA1 hereditary breast cancer.

2. What Are the Signs and Symptoms of Triple-Negative Breast Cancer?

The symptoms of triple-negative breast cancer are similar to those of other breast cancer types and include:

• A lump or mass in the breast detectable by touch or mammogram
• The breast may undergo alterations in form or dimensions
• The skin covering the breast might exhibit dimpling or other modifications
• Nipple discharge or inversion
• Swelling of all or part of a breast
• Skin irritation or changes such as redness These symptoms necessitate prompt medical evaluation to facilitate early detection and treatment.

3. What Causes Triple-Negative Breast Cancer?

The exact causes of TNBC are not fully understood, but the association with BRCA1 and BRCA2 gene mutations is well-documented. These genetic factors may significantly contribute to the development of TNBC, highlighting the importance of genetic counselling and testing in at-risk populations.

4. How is Triple-Negative Breast Cancer Diagnosed?

The reliability of markers to identify triple-negative breast cancer is an area of research. There seem to be several histologic tumour types within TNBC. The selection of such tumours based on ER, PR and HER2 negativity does not mean that they are uniform. In addition, assay techniques for hormone receptors and HER2 are important. An unreliable laboratory will end up having more triple-negative breast cancers! Basal-like breast cancer is also triple negative but has other specific indicators like CK 5/6, and EGFR status. Many current treatment studies for triple-negative breast cancers tend to explore treatment for the whole TNBC group.

5. What Are the Stages of Triple-Negative Breast Cancer?

The staging of TNBC follows the TNM system, which is a standard method used by healthcare providers to describe the extent of cancer's presence and spread.

• Stage 0: Known as carcinoma in situ, this stage is noninvasive, meaning cancer cells are present but confined within the breast ducts and have not spread to surrounding tissue.
• Stage I: This early stage of cancer indicates minimal spread beyond the original tumour site to nearby breast tissue but no involvement of distant organs or significant lymph nodes. Symptoms may also vary, ranging from nipple discharge to redness and swelling.
• Stage II: At this intermediate stage, the tumour might have spread but not to distant parts of the body. Tumours in this stage may also vary in size and may slightly impact nearby lymph nodes.
• Stage III: Often referred to as locally advanced breast cancer, this stage indicates that the cancer has spread more extensively within the breast and surrounding lymph nodes but has not reached distant organs. It encompasses larger tumours that have invaded nearby tissues or numerous lymph nodes. However, do note that according to the Singapore Cancer Registry Annual Report 2020, after five years, breast cancer, along with non-melanoma skin and thyroid cancers, consistently showed some of the highest survival rates among common cancers affecting females.
• Stage IV: This advanced stage, also known as metastatic breast cancer, means that the cancer has spread beyond the breast to other parts of the body, indicating a spread that requires more comprehensive systemic treatment.

6. What is the Survival Rate of Triple-Negative Breast Cancer?

Triple-negative breast cancer recurs more commonly than other types of breast cancer, such as hormone-positive or endocrine-responsive breast cancer. It accounts for a disproportionate percentage of breast cancer deaths. Studies suggest that recurrences tend to occur within the first 5 years after diagnosis for TNBC.

7. How Quickly Does Triple-Negative Breast Cancer Spread?

The ability to spread and metastasise is similar to other breast cancer subtypes, but they have a shorter time to relapse and death. They have been described as aggressive breast cancer because of this. There seems to be a higher likelihood of brain metastasis or spread to the brain for TNBC.

8. What Are the Treatment Options for Triple-Negative Breast Cancer?

Early-stage triple-negative breast cancer can be treated effectively with surgery and many patients may have breast conserving surgery. This is often followed by radiation and adjuvant chemotherapy.

Adjuvant chemotherapy (chemotherapy given after surgery) for triple-negative breast cancer can be highly effective at preventing a recurrence. At OncoCare Cancer Centre, this is what breast cancer specialists would often discuss with patients who present with early triple-negative breast cancer. This is an important modality as there is no option of using endocrine (hormonal) therapy or HER2-directed therapy such as Herceptin.

Current chemotherapy treatment strategies for triple-negative disease include anthracyclines (such as adriamycin, and epirubicin), taxanes (such as paclitaxel, and docetaxel), ixabepilone, platinum agents (cisplatin and carboplatin) and eribulin (Halavan). Triple-negative breast cancers tend to respond well to chemotherapy, but some of the responses seem to be shorter than for the other subtypes.

Genetic counselling should also be considered in triple-negative breast cancer patients particularly younger TNBC patients as some are related to hereditary breast cancer.

9. Is There a Cure for Triple-Negative Breast Cancer?

While TNBC is challenging to treat, ongoing progress made in cancer research is improving the prospects for long-term remission and management, even in advanced cases.

10. What Is the Current Research on Treatments for Triple-Negative Breast Cancer?

Cancer treatment studies of EGFR (epidermal growth factor receptor) inhibition have been proposed with mixed results. Interesting newer agents, such as those targeting the poly(ADP-ribose) polymerase (PARP) inhibitors, have been evaluated and seem to work better for the subgroup related to BRCA1 or BRCA2 mutation carriers.

Find out more about other types of breast cancer such as HER2, invasive lobular and luminal B breast cancer.

“Expert knowledge means better care for cancer”

Written by:

Dr Peter Ang
MBBS (Singapore)
MMed (Int Med)
MRCP (UK)
FAMS (Medical Oncology)